Prognostic value of neutrophil and lymphocyte counts and neutrophil/lymphocyte ratio for predicting death in patients hospitalized for COVID-19.

COVID-19 primarily affects the respiratory system and can cause changes in other systems. Early identification of patients with a higher potential for complications is critical to provide the best possible treatment to reduce the disease's lethality. This study aimed to analyze the behavior of hematologic biomarkers in predicting mortality in patients hospitalized with COVID-19. This retrospective cohort study used data from the medical records of patients hospitalized with COVID-19 between March and August 2020 in two referral hospitals for treatment of the disease in the city of Cuiabá (in the state of Mato Grosso, Brazil). Clinical and laboratory characteristics related to cardiovascular involvement and death during hospitalization were evaluated. Neutrophils, lymphocytes, and monocytes, as well as the neutrophil-to-lymphocyte ratio (NLR) and the monocyte-to-lymphocyte ratio (MRL), were used as potential biomarkers of death. A total of 199 patients were included (male: 113; mean age: 51.4 years). Leukocyte, neutrophil, and lymphocyte counts showed a statistically significant association with death, as did NLR and MRL. Satisfactory accuracy in predicting death was observed for leukocyte, neutrophil, lymphocyte, NLR, and MLR counts. The hematologic biomarkers studied may be useful for prognosticating hospitalized patients for the possibility of death from COVID-19.

Recombinant Bacillus Calmette-Guérin Expressing SARS-CoV-2 Chimeric Protein Protects K18-hACE2 Mice against Viral Challenge.

COVID-19 has accounted for more than 6 million deaths worldwide. Bacillus Calmette-Guérin (BCG), the existing tuberculosis vaccine, is known to induce heterologous effects over other infections due to trained immunity and has been proposed to be a potential strategy against SARS-CoV-2 infection. In this report, we constructed a recombinant BCG (rBCG) expressing domains of the SARS-CoV-2 nucleocapsid and spike proteins (termed rBCG-ChD6), recognized as major candidates for vaccine development. We investigated whether rBCG-ChD6 immunization followed by a boost with the recombinant nucleocapsid and spike chimera (rChimera), together with alum, provided protection against SARS-CoV-2 infection in K18-hACE2 mice. A single dose of rBCG-ChD6 boosted with rChimera associated with alum elicited the highest anti-Chimera total IgG and IgG2c Ab titers with neutralizing activity against SARS-CoV-2 Wuhan strain when compared with control groups. Importantly, following SARS-CoV-2 challenge, this vaccination regimen induced IFN-γ and IL-6 production in spleen cells and reduced viral load in the lungs. In addition, no viable virus was detected in mice immunized with rBCG-ChD6 boosted with rChimera, which was associated with decreased lung pathology when compared with BCG WT-rChimera/alum or rChimera/alum control groups. Overall, our study demonstrates the potential of a prime-boost immunization system based on an rBCG expressing a chimeric protein derived from SARS-CoV-2 to protect mice against viral challenge.

Nursing work environments during covid-19: contributions to develop a technological tool / Ambientes de trabalho de enfermagem durante a covid-19: contribuições para desenvolver uma ferramenta tecnológica / Ambientes de trabajo de enfermería durante covid-19: contribuciones para desarrollar una herramienta tecnológica

Objetivo: avaliar o impacto da COVID-19 nos ambientes de trabalho de enfermagem e desenvolver uma ferramenta tecnológica para avaliar sistematicamente a qualificação desses contextos. Método: pesquisa de método misto realizada em seis hospitais portugueses, com participação de 442 enfermeiros. Utilizou-se um questionário com caracterização sociodemográfica e profissional, a Scale for the Environments Evaluation of Professional Nursing Practice e questões abertas. Resultados: a COVID-19 teve impacto negativo nos componentes Estrutura (ƿ<0,001), Processo (ƿ<0,001) e Resultado (ƿ=0,009) dos ambientes de trabalho de enfermagem. A monitorização da qualidade dos ambientes de trabalho foi apontada como uma estratégia de melhoria. A ferramenta tecnológica desenvolvida permite identificar precocemente as dimensões mais fragilizadas e priorizar melhorias. Conclusão: a COVID-19 repercutiu negativamente nos ambientes de trabalho. A ferramenta tecnológica construída, que tornou mais dinâmica a avaliação dos ambientes de trabalho, além de garantir o envolvimento dos enfermeiros, constitui uma importante ferramenta de gestão.

Objetivo: evaluar el impacto de COVID-19 en los entornos de trabajo de enfermería y desarrollar una herramienta tecnológica para evaluar sistemáticamente la calificación de estos contextos. Método: investigación de método mixto realizada en seis hospitales portugueses, con participación de 442 enfermeros. Se utilizó un cuestionario con caracterización sociodemográfica y profesional, la Scale for the Environments Evaluation of Professional Nursing Practice y cuestiones abiertas. Resultados: La COVID-19 tuvo impacto negativo en los componentes Estructura (ƿ<0,001), Proceso (ƿ<0,001) y Resultado (ƿ=0,009) de los ambientes de trabajo de enfermería. La monitorización de la calidad de los entornos de trabajo fue apuntada como una estrategia de mejora. La herramienta tecnológica desarrollada permite identificar precozmente las dimensiones más fragilizadas y priorizar mejoras. Conclusión: COVID-19 tuvo un impacto negativo en los entornos de trabajo. La herramienta tecnológica construida, que hizo más dinámica la evaluación de los ambientes de trabajo, además de garantizar la participación de los enfermeros, constituye una importante herramienta de gestión.

Objective: to evaluate the impact of COVID-19 on nursing work environments and to develop a technological tool to assess systematically the qualification of these contexts. Method: mixed method research conducted in six Portuguese hospitals, with the participation of 442 nurses. The questionnaire used contained sociodemographic and professional characterization, which was the Scale for the Environments Evaluation of Professional Nursing Practice and open questions. Results: COVID-19 had a negative impact on the components Structure (ƿ<0,001), Process (ƿ<0,001) and Result (ƿ=0,009) of nursing work environments. The monitoring of the quality of the work environments was pointed out as an improvement strategy. The technological tool developed allows identifying the most fragile dimensions early and prioritizing improvements. Final considerations: COVID-19 had a negative impact on work environments. The technological tool built, which made the evaluation of work environments more dynamic, in addition to ensuring the involvement of nurses, is an important management tool.

Integrated Metabolic and Inflammatory Signatures Associated with Severity of, Fatality of, and Recovery from COVID-19.

Severe manifestations of coronavirus disease 2019 (COVID-19) and mortality have been associated with physiological alterations that provide insights into the pathogenesis of the disease. Moreover, factors that drive recovery from COVID-19 can be explored to identify correlates of protection. The cellular metabolism represents a potential target to improve survival upon severe disease, but the associations between the metabolism and the inflammatory response during COVID-19 are not well defined. We analyzed blood laboratorial parameters, cytokines, and metabolomes of 150 individuals with mild to severe disease, of which 33 progressed to a fatal outcome. A subset of 20 individuals was followed up after hospital discharge and recovery from acute disease. We used hierarchical community networks to integrate metabolomics profiles with cytokines and markers of inflammation, coagulation, and tissue damage. Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) promotes significant alterations in the plasma metabolome, whose activity varies according to disease severity and correlates with oxygen saturation. Differential metabolism underlying death was marked by amino acids and related metabolites, such as glutamate, glutamyl-glutamate, and oxoproline, and lipids, including progesterone, phosphocholine, and lysophosphatidylcholines (lysoPCs). Individuals who recovered from severe disease displayed persistent alterations enriched for metabolism of purines and phosphatidylinositol phosphate and glycolysis. Recovery of mild disease was associated with vitamin E metabolism. Data integration shows that the metabolic response is a hub connecting other biological features during disease and recovery. Infection by SARS-CoV-2 induces concerted activity of metabolic and inflammatory responses that depend on disease severity and collectively predict clinical outcomes of COVID-19. IMPORTANCE COVID-19 is characterized by diverse clinical outcomes that include asymptomatic to mild manifestations or severe disease and death. Infection by SARS-CoV-2 activates inflammatory and metabolic responses that drive protection or pathology. How inflammation and metabolism communicate during COVID-19 is not well defined. We used high-resolution mass spectrometry to investigate small biochemical compounds (<1,500 Da) in plasma of individuals with COVID-19 and controls. Age, sex, and comorbidities have a profound effect on the plasma metabolites of individuals with COVID-19, but we identified significant activity of pathways and metabolites related to amino acids, lipids, nucleotides, and vitamins determined by disease severity, survival outcome, and recovery. Furthermore, we identified metabolites associated with acute-phase proteins and coagulation factors, which collectively identify individuals with severe disease or individuals who died of severe COVID-19. Our study suggests that manipulating specific metabolic pathways can be explored to prevent hyperinflammation, organ dysfunction, and death.

From the first to the fourth critical period of COVID-19: what has changed in nursing practice environments in hospital settings?

BACKGROUND: The COVID-19 pandemic reinforced the need to invest in nursing practice environments and health institutions were led to implement several changes. In this sense, this study aimed to analyze the impact of the changes that occurred in nursing practice  environments between the first and fourth critical periods of the pandemic. METHODS: Quantitative, observational study, conducted in a University Hospital, with the participation of 713 registered nurses. Data were collected through a questionnaire with sociodemographic and professional characterization and the Scale for the Environments Evaluation of Professional Nursing Practice, applied at two different points in time: from 1 to 30 June 2020 and from 15 August to 15 September 2021. Data were processed using descriptive and inferential statistics. RESULTS: Overall, the pandemic had a positive impact on nursing practice environments. However, the Process component remained favourable to quality of care, while the Structure and Outcome components only moderately favourable. Nurses working in Medicine Department services showed lower scores in several dimensions of the Structure, Process and Outcome components. On the other hand, nurses working in areas caring for patients with COVID-19 showed higher scores in several dimensions of the Structure, Process and Outcome components. CONCLUSIONS: The pandemic had a positive impact on various dimensions of nursing practice environments, which denotes that regardless of the adversities and moments of crisis that may arise, investment in work environments will have positive repercussions. However, more investment is needed in Medicine Department services, which have historically been characterised by high workloads and structural conditions that make it difficult to promote positive and sustainable workplaces.

A urine-based ELISA with recombinant non-glycosylated SARS-CoV-2 spike protein for detecting anti-SARS-CoV-2 spike antibodies.

Serological assays have been widely used to detect anti-SARS-CoV-2 antibodies, which are generated from previous exposure to the virus or after vaccination. The presence of anti-SARS-CoV-2 Nucleocapsid antibodies was recently reported in patients´ urine using an in-house urine-based ELISA-platform, allowing a non-invasive way to collect clinical samples and assess immune conversion. In the current study, we evaluated and validated another in-house urine-based ELISA for the detection of anti-SARS-CoV-2 Spike antibodies. Three partial recombinant SARS-CoV-2 Spike proteins comprising the Receptor Binding Domain, expressed in eukaryotic or prokaryotic systems, were tested in an ELISA platform against a panel of over 140 urine and paired serum samples collected from 106 patients confirmed positive for SARS-CoV-2 by qRT-PCR. The key findings from our study were that anti-SARS-CoV-2 Spike antibodies could be detected in urine samples and that the prokaryotic expression of the rSARS-CoV-2 Spike protein was not a barrier to obtain relatively high serology efficiency for the urine-based assay. Thus, use of a urine-based ELISA assay with partial rSARS-CoV-2 Spike proteins, expressed in a prokaryotic system, could be considered as a convenient tool for screening for the presence of anti-SARS-CoV-2 Spike antibodies, and overcome the difficulties arising from sample collection and the need for recombinant proteins produced with eukaryotic expression systems.

Pathways to wheat self-sufficiency in Africa.

A growing urban population and dietary changes increased wheat import bills in Africa to 9% per year. Though wheat production in the continent has been increasing over the past decades, to varying degrees depending on regions, this has not been commensurate with the rapidly increasing demand for wheat. Analyses of wheat yield gaps show that there is ample opportunity to increase wheat production in Africa through improved genetics and agronomic practices. Doing so would reduce import dependency and increase wheat self-sufficiency at national level in many African countries. In view of the uncertainties revealed by the global COVID-19 pandemic, extreme weather events, and world security issues, national policies in Africa should re-consider the value of self-sufficiency in production of staple food crops, specifically wheat. This is particularly so for areas where water-limited wheat yield gaps can be narrowed through intensification on existing cropland and judicious expansion of rainfed and irrigated wheat areas. Increasing the production of other sources of calories (and proteins) should also be considered to reduce dependency on wheat imports.

Impact of COVID-19 on professional nursing practice environments and patient safety culture.

AIM: To analyse the impact of COVID-19 on professional nursing practice environments and patient safety culture. BACKGROUND: The relationship between work environments and patient safety has been internationally recognized. In 2020, the pandemic imposed enormous challenges, yet the impact on these variables remains unknown. METHOD: This is a quantitative observational study, conducted in a Portuguese hospital, with 403 registered nurses. A self-completion questionnaire was used. RESULTS: The impact on the Structure and Outcome components of nursing professional practice environments was positive. Although the Process component remained favourable to quality of care, a negative trend was confirmed in almost all dimensions. The results regarding safety culture showed weaknesses; 'teamwork within units' was the only dimension that maintained a positive culture. CONCLUSION: Positive responses regarding patient safety were significantly associated with the quality of the nursing professional practice environment. The need to invest in all dimensions of safety culture emerges to promote positive professional environments. IMPLICATIONS FOR NURSING MANAGEMENT: Improving professional nursing practice environments can be achieved through managers' investment in the participation and involvement of nurses in the policies and functioning of institutions, as well as promoting an open, fair and participatory safety culture that encourages reporting events and provides adequate support for professionals.

Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

Differential requirement of neutralizing antibodies and T cells on protective immunity to SARS-CoV-2 variants of concern.

The current COVID-19 vaccines protect against severe disease, but are not effective in controlling replication of the Variants of Concern (VOCs). Here, we used the existing pre-clinical models of severe and moderate COVID-19 to evaluate the efficacy of a Spike-based DNA vaccine (pCTV-WS) for protection against different VOCs. Immunization of transgenic (K18-hACE2) mice and hamsters induced significant levels of neutralizing antibodies (nAbs) to Wuhan and Delta isolates, but not to the Gamma and Omicron variants. Nevertheless, the pCTV-WS vaccine offered significant protection to all VOCs. Consistently, protection against lung pathology and viral load to Wuhan or Delta was mediated by nAbs, whereas in the absence of nAbs, T cells controlled viral replication, disease and lethality in mice infected with either the Gamma or Omicron variants. Hence, considering the conserved nature of CD4 and CD8 T cell epitopes, we corroborate the hypothesis that induction of effector T-cells should be a main goal for new vaccines against the emergent SARS-CoV-2 VOCs.

[Impact of the COVID-19 pandemic on percutaneous coronary interventions in Portugal]. / Impacto da pandemia por COVID-19 nas intervenções coronárias percutâneas em Portugal.

INTRODUCTION: The COVID-19 pandemic has imposed an unprecedented burden on healthcare systems worldwide, changing the profile of interventional cardiology activity. OBJECTIVES: To quantify and compare the number of percutaneous coronary interventions (PCIs) performed for acute and chronic coronary syndromes during the first COVID-19 outbreak with the corresponding period in previous years. METHODS: Data on PCI from the prospective multicenter Portuguese Registry on Interventional Cardiology (RNCI) were used to analyze changes in PCI for ST-elevation myocardial infarction (STEMI), non-ST-elevation acute coronary syndromes (NSTE-ACS) and chronic coronary syndromes (CCS). The number of PCIs performed during the initial period of the COVID-19 outbreak in Portugal, from March 1 to May 2, 2020, was compared with the mean frequency of PCIs performed during the corresponding period in the previous three years (2017-2019). RESULTS: The total number of PCIs procedures was significantly decreased during the initial COVID-19 outbreak in Portugal (-36%, p<0.001). The reduction in PCI procedures for STEMI, NSTE-ACS and CCS was, respectively, -25% (p<0.019), -20% (p<0.068) and -59% (p<0.001). CONCLUSIONS: Compared with the corresponding period in the previous three years, the number of PCI procedures performed for STEMI and CCS decreased markedly during the first wave of the COVID-19 pandemic in Portugal.

The Cytoplasmic Domain of the SARS-CoV-2 Envelope Protein Assembles into a ß-Sheet Bundle in Lipid Bilayers.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) envelope (E) protein forms a pentameric ion channel in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment (ERGIC) of the infected cell. The cytoplasmic domain of E interacts with host proteins to cause virus pathogenicity and may also mediate virus assembly and budding. To understand the structural basis of these functions, here we investigate the conformation and dynamics of an E protein construct (residues 8-65) that encompasses the transmembrane domain and the majority of the cytoplasmic domain using solid-state NMR. 13C and 15N chemical shifts indicate that the cytoplasmic domain adopts a ß-sheet-rich conformation that contains three ß-strands separated by turns. The five subunits associate into an umbrella-shaped bundle that is attached to the transmembrane helices by a disordered loop. Water-edited NMR spectra indicate that the third ß-strand at the C terminus of the protein is well hydrated, indicating that it is at the surface of the ß-bundle. The structure of the cytoplasmic domain cannot be uniquely determined from the inter-residue correlations obtained here due to ambiguities in distinguishing intermolecular and intramolecular contacts for a compact pentameric assembly of this small domain. Instead, we present four structural topologies that are consistent with the measured inter-residue contacts. These data indicate that the cytoplasmic domain of the SARS-CoV-2 E protein has a strong propensity to adopt ß-sheet conformations when the protein is present at high concentrations in lipid bilayers. The equilibrium between the ß-strand conformation and the previously reported α-helical conformation may underlie the multiple functions of E in the host cell and in the virion.

The Impact of COVID-19 on Nursing Practice Environments in Mental Health and Psychiatric Units

The rapid evolution of the pandemic did not allow for the preparation of different clinical settings. For this reason, the evaluation of the repercussions and the investment in improvement strategies has become important. The aim of this paper was to analyse the impact of COVID-19 on nursing practice environments in Mental Health and Psychiatric Units of three hospitals, through a quantitative observational study. Data collection was carried out through a questionnaire with inquiries on the characterization and the SEE-Nursing Practice. We confirmed a positive impact on the Structure and Outcome components of the nursing practice environments and a negative impact on the Process component.

Distress facing increased genetic risk of cancer: The role of social support and emotional suppression.

OBJECTIVES: Healthy individuals from hereditary cancer families undergoing genetic testing for cancer susceptibility (GTC) report more distress when they perceive their social support as low and suppress their emotions. This study aimed to explore how suppressing emotions and perceiving others as unsupportive are related with cancer-risk distress. METHODS: We performed a regression-based mediation analysis to assess if expressive suppression mediates or is mediated by perceived social support in the relation with cancer-risk distress. Participants were 125 healthy adults aged over 18 (M = 36.07, SD = 12.86), mostly female (72,4%), who undergone GTC to assess the presence of hereditary breast and ovarian cancer or Lynch syndromes. RESULTS: Controlling for age and gender, we found a moderate size indirect effect of social support on cancer-risk distress through expressive suppression (ß = -0.095) and a direct effect of expressive suppression on cancer-risk distress. CONCLUSIONS: When healthy individuals from hereditary cancer families perceive their social network as less responsive, they tend to not express their emotions, which relates to increased distress facing GTC. PRACTICE IMPLICATIONS: Practitioners may assess cancer-risk related distress before the GTC and offer distressed individuals interventions focused on changing emotion regulation strategies in a safe group context.

SARS-CoV-2 Envelope Protein Forms Clustered Pentamers in Lipid Bilayers.

The SARS-CoV-2 envelope (E) protein is a viroporin associated with the acute respiratory symptoms of COVID-19. E forms cation-selective ion channels that assemble in the lipid membrane of the endoplasmic reticulum Golgi intermediate compartment. The channel activity of E is linked to the inflammatory response of the host cell to the virus. Like many viroporins, E is thought to oligomerize with a well-defined stoichiometry. However, attempts to determine the E stoichiometry have led to inconclusive results and suggested mixtures of oligomers whose exact nature might vary with the detergent used. Here, we employ 19F solid-state nuclear magnetic resonance and the centerband-only detection of exchange (CODEX) technique to determine the oligomeric number of E's transmembrane domain (ETM) in lipid bilayers. The CODEX equilibrium value, which corresponds to the inverse of the oligomeric number, indicates that ETM assembles into pentamers in lipid bilayers, without any detectable fraction of low-molecular-weight oligomers. Unexpectedly, at high peptide concentrations and in the presence of the lipid phosphatidylinositol, the CODEX data indicate that more than five 19F spins are within a detectable distance of about 2 nm, suggesting that the ETM pentamers cluster in the lipid bilayer. Monte Carlo simulations that take into account peptide-peptide and peptide-lipid interactions yielded pentamer clusters that reproduced the CODEX data. This supramolecular organization is likely important for E-mediated virus assembly and budding and for the channel function of the protein.

Post-COVID-19 superior mesenteric artery and jejunal branches thromboembolism.

The World Health Organization has declared the novel coronavirus disease 2019 (COVID-19) a global public health emergency. Despite the predominating respiratory symptoms occurring in COVID-19, thrombosis can occur in some patients, with morbidity and mortality increase due to the respiratory worsening. This article reports the case of a 62-year-old man with a flu-like illness that was diagnosed as COVID-19 by RT-PCR of SARS-CoV-2. After three weeks, he subsequently developed abdominal pain in addition to bloating, nausea, and vomiting. He underwent exploratory laparotomy after imaging tests suggested mesenteric ischemia. Intestinal ischemia was evident, due to the absence of flow in the superior mesenteric artery and jejunal branches. Embolectomy and enterectomy were performed and they resulted in a favorable outcome, with clinical improvement. This case adds data to the limited literature on extrapulmonary complications of COVID-19, notably those related to thromboembolic events.

La Organización Mundial de la Salud ha declarado la enfermedad del nuevo coronavirus 2019 (COVID-19) una emergencia de salud pública mundial. A pesar de los síntomas respiratorios predominantes en COVID-19, la trombosis puede ocurrir en algunos pacientes, con un aumento de la morbimortalidad debido al empeoramiento respiratorio. Presentamos el caso de un hombre de 62 años con enfermedad similar a la gripe que fue diagnosticada como COVID-19 por RT-PCR de SARS-CoV-2. Después de tres semanas, desarrolló dolor abdominal además de hinchazón, náuseas y vómitos. Fue sometido a laparotomía exploradora luego de que las pruebas de imagen sugirieran isquemia mesentérica. Se evidenció isquemia intestinal por ausencia de flujo en la arteria mesentérica superior y ramas yeyunales. Se realizó embolectomía y enterectomía con evolución favorable, con mejoría clínica. Este caso añade datos a la limitada literatura sobre las complicaciones extrapulmonares del COVID-19, en particular las relacionadas con eventos tromboembólicos.

Impact of climate-driven temperature increase on inland aquaculture: Application to land-based production of common carp (Cyprinus carpio L.).

Climate change will expose the food-producing sector to a range of challenges. Inland aquaculture farms are particularly vulnerable, due to the difficulty in changing their location, and therefore require specific tools to predict the influence of direct and indirect effects on production, environment and economic feasibility. The objective of our study was to apply a simple set of models to produce a set of growth, risk and suitability maps for stakeholders within the common carp sector in Poland, to assist decision-making under two different scenarios of climate change: a moderate situation (RCP 4.5) and an extreme situation (RCP 8.5). We used present (2000-2019) and future projections (2080-2099) for water surface temperature based on land surface temperature data from regionally downscaled climate models to draw maps to: (i) show optimal temperature conditions for carp growth, (ii) assess risk of disease outbreak caused by three important common carp pathogens: Cyprinid herpesvirus 3 (CyHV-3), carp oedema virus (CEV) and spring viremia of carp (SVCV) and (iii) predict potential suitability changes of carp farming in Poland. The study identified areas with the most and least favourable temperature conditions for carp growth, as well as those areas with the highest/lowest number of days with suitable temperatures for virus infection. These suitability maps showed the combined effect of direct and indirect effects of climate change projections under RCP 8.5 and RCP 4.5 scenarios. The approach applied herein will be of use worldwide for analysing the risks of temperature increase to land-based aquaculture, and the results presented are important for carp farmers in Poland and elsewhere, industry in general, and government stakeholders, to understand the direct and indirect effects of climate change on the triple bottom line of people, planet, and profit.

A novel vaccine based on SARS-CoV-2 CD4+ and CD8+ T cell conserved epitopes from variants Alpha to Omicron.

COVID-19 caused, as of September, 1rst, 2022, 599,825,400 confirmed cases, including 6,469,458 deaths. Currently used vaccines reduced severity and mortality but not virus transmission or reinfection by different strains. They are based on the Spike protein of the Wuhan reference virus, which although highly antigenic suffered many mutations in SARS-CoV-2 variants, escaping vaccine-generated immune responses. Multiepitope vaccines based on 100% conserved epitopes of multiple proteins of all SARS-CoV-2 variants, rather than a single highly mutating antigen, could offer more long-lasting protection. In this study, a multiepitope multivariant vaccine was designed using immunoinformatics and in silico approaches. It is composed of highly promiscuous and strong HLA binding CD4+ and CD8+ T cell epitopes of the S, M, N, E, ORF1ab, ORF 6 and ORF8 proteins. Based on the analysis of one genome per WHO clade, the epitopes were 100% conserved among the Wuhan-Hu1, Alpha, Beta, Gamma, Delta, Omicron, Mµ, Zeta, Lambda and R1 variants. An extended epitope-conservancy analysis performed using GISAID metadata of 3,630,666 SARS-CoV-2 genomes of these variants and the additional genomes of the Epsilon, Lota, Theta, Eta, Kappa and GH490 R clades, confirmed the high conservancy of the epitopes. All but one of the CD4 peptides showed a level of conservation greater than 97% among all genomes. All but one of the CD8 epitopes showed a level of conservation greater than 96% among all genomes, with the vast majority greater than 99%. A multiepitope and multivariant recombinant vaccine was designed and it was stable, mildly hydrophobic and non-toxic. The vaccine has good molecular docking with TLR4 and promoted, without adjuvant, strong B and Th1 memory immune responses and secretion of high levels of IL-2, IFN-γ, lower levels of IL-12, TGF-ß and IL-10, and no IL-6. Experimental in vivo studies should validate the vaccine's further use as preventive tool with cross-protective properties.

CARACTERÍSTICAS CLÍNICAS E SOCIODEMOGRÁFICAS DA COVID-19 EM JOVENS COM DESFECHO FATAL NA 1ª VERSUS 2ª ONDA: UM ESTUDO COMPARATIVO

Introdução A pandemia da COVID-19 tornou-se o maior problema de saúde pública dos últimos 100 anos, apresentando ondas desde que iniciou a propagação. As características sociodemográficas e clínicas possuem variações entre as ondas e entre os países. Ao comparar a Primeira Onda (PO) com a Segunda Onda (SO), uma inconstância nos relatos é observada. Ainda assim, um importante dado comum é a maior frequência de pessoas menores de 50 anos acometidos na SO, inclusive, indo a óbito. Objetivo Analisar a diferença básica entre a PO e a SO com foco local. Além dessa diferenciação geral, o presente trabalho também objetiva avaliar as características clínicas e sociodemográficas dos pacientes menores que 50 anos e que evoluíram com desfecho fatal em ambas as ondas. Método Trata-se de uma coorte retrospectiva, realizada em um hospital público de referência estadual, que coletou dados de desfecho hospitalar e idade para todos os pacientes internados por COVID-19, além de dados sociodemográficos e clínicos de todos os pacientes menores de 50 anos e que evoluíram a óbito na unidade durante o período de 01/03/2020 a 01/06/2021. Para o tratamento estatístico foram utilizados o Teste de Qui-quadrado, para variáveis categóricas, e o Teste de Mann-Whitney, para variáveis numéricas. Resultados Dentro do período proposto, foram coletados dados de 3.875 pacientes, sendo 230 os pacientes menores de 50 anos e com desfecho fatal (113 na PO e 117 na SO). Em relação à PO, a SO apresentou menor letalidade (PO:29%, SO:22%;p < 0,01) e menor média de idade (diferença de 5,25 anos;p < 0,01). Em relação ao subgrupo de interesse, houve pouca diferença estatisticamente significante entre as ondas, exceto pelo Tempo de Internamento Hospitalar (de 9 para 13,5 dias, p < 0,01), incidência de Diabetes mellitus (de 29,2% para 16,2%, p < 0,01) e Hiperglicemia hospitalar (de 54% para 71,8%;p < 0,01). Conclusão A SO foi caracterizada por menor letalidade e acometimento de pacientes mais jovens. Ao estratificar para o subgrupo de pacientes menores que 50 anos e com desfecho fatal, observou-se uma segunda onda composta principalmente por homens mais saudáveis, além de uma doença menos severa. O surgimento da variante gamma, a curva de aprendizado no manejo da doença entre as ondas, uma primeira onda mais letal e severa e a maior disponibilidade de recursos hospitalares no segundo momento podem ter contribuído para as diferenças observadas. Ag. Financiadora CNPQ.

The Severity of COVID-19 Affects the Plasma Soluble Levels of the Immune Checkpoint HLA-G Molecule.

The non-classical histocompatibility antigen G (HLA-G) is an immune checkpoint molecule that has been implicated in viral disorders. We evaluated the plasma soluble HLA-G (sHLA-G) in 239 individuals, arranged in COVID-19 patients (n = 189) followed up at home or in a hospital, and in healthy controls (n = 50). Increased levels of sHLA-G were observed in COVID-19 patients irrespective of the facility care, gender, age, and the presence of comorbidities. Compared with controls, the sHLA-G levels increased as far as disease severity progressed; however, the levels decreased in critically ill patients, suggesting an immune exhaustion phenomenon. Notably, sHLA-G exhibited a positive correlation with other mediators currently observed in the acute phase of the disease, including IL-6, IL-8 and IL-10. Although sHLA-G levels may be associated with an acute biomarker of COVID-19, the increased levels alone were not associated with disease severity or mortality due to COVID-19. Whether the SARS-CoV-2 per se or the innate/adaptive immune response against the virus is responsible for the increased levels of sHLA-G are questions that need to be further addressed.